Chromatin interaction-based annotation of regulatory elements reveals dynamic promoter-enhancer interactions in lymphocyte development

Summary: Stage- and lineage-specific gene expression patterns are controlled by a complex interplay between transcription factors, the epigenetic landscape, and the three-dimensional (3D) structure of the DNA. The 3D structure allows for the formation of DNA loops that juxtaposition distal regulator...

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Main Authors: Johanna Tingvall-Gustafsson, Christina T. Jensen, Jonas Ungerbäck, Mikael Sigvardsson
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225011162
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author Johanna Tingvall-Gustafsson
Christina T. Jensen
Jonas Ungerbäck
Mikael Sigvardsson
author_facet Johanna Tingvall-Gustafsson
Christina T. Jensen
Jonas Ungerbäck
Mikael Sigvardsson
author_sort Johanna Tingvall-Gustafsson
collection DOAJ
description Summary: Stage- and lineage-specific gene expression patterns are controlled by a complex interplay between transcription factors, the epigenetic landscape, and the three-dimensional (3D) structure of the DNA. The 3D structure allows for the formation of DNA loops that juxtaposition distal regulatory elements to the promoters, allowing for tight control of gene expression. Developing a tool to facilitate the exploration of complex gene regulatory networks based on chromosome configuration data in early lymphocytes, we show that lineage-specific transcription factors target regulatory elements annotated to both lineage-specific and broadly expressed genes. Several regulatory elements annotated to lineage-specific genes were also annotated to alternative promoters in a context-dependent manner, revealing a highly complex interplay between promoters and DREs in early lymphocyte development. These data highlight how efficient annotation procedures for linking distal regulatory elements to target genes provide valuable insights into gene regulatory networks.
format Article
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institution Kabale University
issn 2589-0042
language English
publishDate 2025-07-01
publisher Elsevier
record_format Article
series iScience
spelling doaj-art-59da59b346254c37b2ed22582057b4d02025-08-20T03:50:21ZengElsevieriScience2589-00422025-07-0128711285510.1016/j.isci.2025.112855Chromatin interaction-based annotation of regulatory elements reveals dynamic promoter-enhancer interactions in lymphocyte developmentJohanna Tingvall-Gustafsson0Christina T. Jensen1Jonas Ungerbäck2Mikael Sigvardsson3Division of Molecular Hematology, Lund University, Lund, Sweden; Division of Molecular Medicine and Virology, Linköping University, Lab 1 Level 13, 58135 Linköping, SwedenDivision of Molecular Hematology, Lund University, Lund, SwedenDivision of Molecular Hematology, Lund University, Lund, SwedenDivision of Molecular Hematology, Lund University, Lund, Sweden; Division of Molecular Medicine and Virology, Linköping University, Lab 1 Level 13, 58135 Linköping, Sweden; Allen Institute for Immunology, Seattle, WA, USA; Corresponding authorSummary: Stage- and lineage-specific gene expression patterns are controlled by a complex interplay between transcription factors, the epigenetic landscape, and the three-dimensional (3D) structure of the DNA. The 3D structure allows for the formation of DNA loops that juxtaposition distal regulatory elements to the promoters, allowing for tight control of gene expression. Developing a tool to facilitate the exploration of complex gene regulatory networks based on chromosome configuration data in early lymphocytes, we show that lineage-specific transcription factors target regulatory elements annotated to both lineage-specific and broadly expressed genes. Several regulatory elements annotated to lineage-specific genes were also annotated to alternative promoters in a context-dependent manner, revealing a highly complex interplay between promoters and DREs in early lymphocyte development. These data highlight how efficient annotation procedures for linking distal regulatory elements to target genes provide valuable insights into gene regulatory networks.http://www.sciencedirect.com/science/article/pii/S2589004225011162Chromosome organizationMolecular geneticsEpigeneticsComponents of the immune system
spellingShingle Johanna Tingvall-Gustafsson
Christina T. Jensen
Jonas Ungerbäck
Mikael Sigvardsson
Chromatin interaction-based annotation of regulatory elements reveals dynamic promoter-enhancer interactions in lymphocyte development
iScience
Chromosome organization
Molecular genetics
Epigenetics
Components of the immune system
title Chromatin interaction-based annotation of regulatory elements reveals dynamic promoter-enhancer interactions in lymphocyte development
title_full Chromatin interaction-based annotation of regulatory elements reveals dynamic promoter-enhancer interactions in lymphocyte development
title_fullStr Chromatin interaction-based annotation of regulatory elements reveals dynamic promoter-enhancer interactions in lymphocyte development
title_full_unstemmed Chromatin interaction-based annotation of regulatory elements reveals dynamic promoter-enhancer interactions in lymphocyte development
title_short Chromatin interaction-based annotation of regulatory elements reveals dynamic promoter-enhancer interactions in lymphocyte development
title_sort chromatin interaction based annotation of regulatory elements reveals dynamic promoter enhancer interactions in lymphocyte development
topic Chromosome organization
Molecular genetics
Epigenetics
Components of the immune system
url http://www.sciencedirect.com/science/article/pii/S2589004225011162
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AT christinatjensen chromatininteractionbasedannotationofregulatoryelementsrevealsdynamicpromoterenhancerinteractionsinlymphocytedevelopment
AT jonasungerback chromatininteractionbasedannotationofregulatoryelementsrevealsdynamicpromoterenhancerinteractionsinlymphocytedevelopment
AT mikaelsigvardsson chromatininteractionbasedannotationofregulatoryelementsrevealsdynamicpromoterenhancerinteractionsinlymphocytedevelopment